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Whipple disease: intestinal infiltrating cells exhibit a transcriptional pattern of M2/alternatively activated

Benoît Desnues1, Hubert Lepidi, Didier Raoult

  • 1Unité des Rickettsies, Centre National de la Recherche Scientifique, Institut Fédératif de Recherche 48, Université de la Méditerranée, Faculté de Médecine, Marseille, France.

The Journal of Infectious Diseases
|October 6, 2005
PubMed

Insights

Whipple disease (WD) involves Tropheryma whipplei bacteria and foamy macrophages. Gene expression analysis reveals M2 macrophage activation in intestinal lesions, suggesting a T helper 2 response contributes to WD.

Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • Whipple disease (WD) is a rare systemic infection caused by Tropheryma whipplei.
  • It is characterized by foamy macrophages containing periodic acid-Schiff-positive inclusions in various tissues, particularly the intestinal lamina propria.

Purpose of the Study:

  • To investigate the gene-expression profile of macrophages within intestinal lesions of a patient diagnosed with Whipple disease.
  • To elucidate the specific macrophage activation phenotype and its role in the disease's pathophysiology.

Main Methods:

  • Gene expression profiling using microarray analysis.
  • Validation of key gene expression changes through real-time polymerase chain reaction (PCR).
  • Analysis of macrophage phenotype based on transcriptional patterns.

Main Results:

  • Significant up-regulation of genes including CCL18, cathepsins, scavenger receptor, interleukin-10, and lipid metabolites in intestinal lesions.
  • The observed transcriptional pattern strongly correlates with the M2/alternatively activated macrophage phenotype.
  • Identification of specific molecular markers associated with WD pathogenesis.

Conclusions:

  • The gene-expression profile of macrophages in Whipple disease intestinal lesions indicates an M2 activation state.
  • A T helper 2 (Th2) immune response in the intestinal microenvironment is implicated in the pathophysiological mechanisms of Whipple disease.
  • These findings provide novel insights into the immune dysregulation underlying WD.

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